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Purpose: The globally increasing older population raises concerns about age-related conditions, including cognitive impairment and depressive symptoms. In Latin America, nearly one-third of the population is affected by either of these conditions. However, data investigating the association between cognitive impairment and depressive symptoms, particularly in Brazil, are limited to small-scale studies that have not carefully examined the critical effects of variables such as education level and socioeconomic status on this relationship. We aimed at exploring this association in a representative population-based cohort. Methods: We used the Brazilian Longitudinal Study of Aging (ELSI-BRAZIL) database to examine the relationship between depressive symptoms and cognitive impairment in Brazilian older adults, adjusted for potential confounders. Direct acyclic graphs and multivariable linear regression were used to build our model. Depressive symptoms were measured using a short version of the Center for Epidemiologic Studies Scale (CES D-8), and combined memory recall test as a surrogate of cognitive impairment. Results: The study included 8280 participants. Only education level was identified as a confounder for the relationship between memory loss and depressive symptoms. After adjusting for age, sex, and education level, there was strong evidence for a negative association between depressive symptoms and memory performance. For every 5-unit increase in the CES D-8 score, there was a reduction in memory capacity, translating to a loss of approximately one word in the combined words recall test (mean - 0.18, 95% CI -0.22; -0.15, P < 0.001). In addition, we found strong evidence for an interaction between socioeconomic status and depressive symptoms. Subjects belonging to medium socioeconomic status (SES) showed more pronounced memory decline, when compared to those with lower SES (mean - 0.28, 95% CI -0.42 to -0.14, P < 0.001). Conclusions: In adults aged over 50, after adjusting for sex, age, and educational level, a 5-unit increase in CES D-8 score is associated with loss of one point in the combined memory recall test. This association seems to be confounded by educational level and significantly modified by socioeconomic status.
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INTRODUCTION: Tuberous sclerosis complex is a rare genetic disorder leading to the growth of hamartomas in multiple organs, including cardiac rhabdomyomas. Children with symptomatic cardiac rhabdomyoma require frequent admissions to intensive care units, have major complications, namely, arrhythmias, cardiac outflow tract obstruction and heart failure, affecting the quality of life and taking on high healthcare cost. Currently, there is no standard pharmacological treatment for this condition, and the management includes a conservative approach and supportive care. Everolimus has shown positive effects on subependymal giant cell astrocytomas, renal angiomyolipoma and refractory seizures associated with tuberous sclerosis complex. However, evidence supporting efficacy in symptomatic cardiac rhabdomyoma is limited to case reports. The ORACLE trial is the first randomised clinical trial assessing the efficacy of everolimus as a specific therapy for symptomatic cardiac rhabdomyoma. METHODS: ORACLE is a phase II, prospective, randomised, placebo-controlled, double-blind, multicentre protocol trial. A total of 40 children with symptomatic cardiac rhabdomyoma secondary to tuberous sclerosis complex will be randomised to receive oral everolimus or placebo for 3 months. The primary outcome is 50% or more reduction in the tumour size related to baseline. As secondary outcomes we include the presence of arrhythmias, pericardial effusion, intracardiac obstruction, adverse events, progression of tumour reduction and effect on heart failure. CONCLUSIONS: ORACLE protocol addresses a relevant unmet need in children with tuberous sclerosis complex and cardiac rhabdomyoma. The results of the trial will potentially support the first evidence-based therapy for this condition.